Posted by King Vultan on March 25, 2004, at 7:52:14
In reply to Concurrent use of 2 Drugs Metabolized by 2d6 Enzym, posted by Lightshifter on March 24, 2004, at 20:37:33
> I emailed this to Dr. Bob but I guess he can no longer get to reply to these directly. If anyone has any credible information on what happens when 2 drugs are given at the same time when they are both metabolized by the same enzyme (2d6) I'd appreciate a response... (Strattera and Nortryptaline are the 2 drugs being used at same time.)
>
> Dear Dr. Bob,
>
> I've been trying to get an answer to a question regarding the metabolizing of multiple drugs by the CYP450-2D6 enzyme.
>
> Can you tell me if drug metabolism is decreased when multiple drugs are used that are metabolized by the same enzyme (2D6)? I have a friend who has been prescribed multiple drugs which are metabolized by it and was wondering if that may be reducing the metabolization and therefore the effectiveness of the drugs due to them competing for the same metabolizer.
>
> I'd appreciate any help you might be able to provide and if you know of any links where this may be discussed I'd love to review the information.
>
> Thanks For Your Help,
>
> Dan Hunt
>
>No, the problem generally winds up being just the opposite in this type of situation, as it is common for the older antidepressants to inhibit the 2D6 enzyme. When this happens, the enzyme becomes tied up with one drug and is unable to properly metabolize the other. However, rather than reduce the effectiveness of the other drug, the strength winds up being magnified, as the drug stays in the bloodstream longer than normal, has a higher peak plasma level, and a higher sustained blood plasma level.
It may help to clarify what's going on by pointing out that in most cases, the metabolism in the liver is not necessary for these drugs to function. Rather, metabolism by mechanisms such as the CYP-450 enzyme system is what allows the body to get rid of the drugs, usually by hydroxylating them to increase their water solubility and allowing the kidneys to excrete them. A drug such as nortriptyline does not need to be metabolized into another form to be effective, but once it is acted on by the CYP-450 enzyme system, being metabolized to 10-hydroxy-nortriptyline, for instance, it is removed from the body in fairly short order.
That be said, you are correct that both Strattera and nortriptyline are 2D6 substrates, but only nortriptyline is a 2D6 inhibitor. The secondary amine tricyclics are only weak to moderate inhibitors, however, so I would not expect this to be a giant problem, the Strattera blood plasma levels probably going up moderately. More serious are problems involving the reverse, where a tricyclic is combined with a strong 2D6 inhibitor such as Prozac or Paxil. In those cases, levels of the tricyclic can rise to dangerous levels, as these drugs are cardiotoxic and lethal in overdose.
Todd
poster:King Vultan
thread:327939
URL: http://www.dr-bob.org/babble/20040325/msgs/328126.html